This paper follows the circuitous path of theories concerning the origins of viruses from the early years of the twentieth century until the present, considering RNA viruses in particular. I focus on three periods during which new understandings of the nature of viruses guided the construction and reconstruction of origin hypotheses. During the first part of the twentieth century, viruses were mostly viewed from within the framework of bacteriology and the discussion of origin centered on the “degenerative” or the “retrograde (...) evolution theory.” However, concomitantly, in the context of origin-of-life theorizing, the notion that viruses are vestiges of a prebiotic world was also being contemplated. In the 1960s the idea that viruses were genetic elements that “escaped” from cells became prevalent. These traditional hypotheses are being revisited nowadays by evolutionary virologists, who have placed them within a new conceptual framework that is supported by cutting-edge genomic and proteomic data. Two current, opposing scenarios of virus origin are presented. The philosophical dimensions of “revisiting” the original hypotheses are briefly discussed. (shrink)

RNAs can do many things. They can store information, act in the world, and respond to the world. Because of these capabilities biologists have proposed a primordial ‘RNA world’ in which RNA, rather than DNA, performed the central role of replicator and repository of adaptive information. Deacon dismisses this hypothesis because replication is not about anything and because the structure of replicating molecules cannot contain information about the environment. I dispute both claims. An RNA and its opposite-sense (...) complement represent each other and, by two rounds of complementation, represent themselves. Although nucleic acid sequences do not change in response to their present environment, these sequences embody information about ancestral environments via the selective filtering of alternative sequences in those environments. Nucleic acid sequences are the textual record of what has worked in the past. (shrink)

Our knowledge about the functional diversity and importance of RNA in biology has grown enormously over the past three decades and has driven efforts to develop better tools to characterize RNAs. Amongst these tools are methods for preparing specifically labeled or chemically modified RNAs, which are essential for basic research, biomedical, and clinical applications. Understanding the potential and limits of these different RNA synthesis and labeling strategies is important in deciding how to approach the preparation of a particular RNA molecule. (...) Here, we review these various labeling methods and future directions of the field. (shrink)

Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin‐converting enzyme (ACE) is the central component of endocrine and local tissue renin–angiotensin systems (RAS), which also regulate diverse aspects of whole‐body metabolism and mitochondrial function (partly through altering mitochondrial UCP expression). We show that ACE expression also appears to be regulated by mitochondrial UCPs. In genetic analysis of two unrelated populations (healthy young UK men and Scandinavian diabetic patients) serum ACE (sACE) activity was significantly higher amongst UCP3‐55C (rather than (...) T) and UCP2 I (rather than D) allele carriers. RNA interference against UCP2 in human umbilical vein endothelial cells reduced UCP2 mRNA sixfold (P < 0·01) whilst increasing ACE expression within a physiological range (<1·8‐fold at 48 h; P < 0·01). Our findings suggest novel hypotheses. Firstly, cellular feedback regulation may occur between UCPs and ACE. Secondly, cellular UCP regulation of sACE suggests a novel means of crosstalk between (and mutual regulation of) cellular and endocrine metabolism. This might partly explain the reduced risk of developing diabetes and metabolic syndrome with RAS antagonists and offer insight into the origins of cardiovascular disease in which UCPs and ACE both play a role. (shrink)

Modern cells present no signs of a putative prebiotic RNA world. However, RNA coding is not a sine qua non for the accumulation of catalytic polypeptides. Thus, cellular proteins spontaneously fold into active structures that are resistant to proteolysis. The law of mass action suggests that binding domains are stabilized by specific interactions with their substrates. Random polypeptide synthesis in a prebiotic world has the potential to initially produce only a very small fraction of polypeptides that can fold (...) spontaneously into catalytic domains. However, that fraction can be enriched by proteolytic activities that destroy the unfolded polypeptides and regenerate amino acids that can be recycled into polypeptides. In this open system scenario the stable domains that accumulate and the chemical environment in which they are accumulated are linked through self coding of polypeptide structure. Such open polypeptide systems may have been the precursors to the cellular ribonucleoprotein (RNP) world that evolved subsequently. (shrink)

Life appears to be a natural property of matter, but the problem of its origin only arose after early scientists refuted continuous spontaneous generation. There is no chance of life arising ‘all at once’, we need the standard scientific incremental explanation with large numbers of small steps, an approach used in both physical and evolutionary sciences. The necessity for considering both theoretical and experimental approaches is emphasized. After describing basic principles that are available (including the Darwin-Eigen cycle), the search for (...) origins is considered under four main themes. These are the RNA-world hypothesis; potential intermediates between an RNA-world and a modern world via the evolution of protein synthesis and then of DNA; possible alternatives to an RNA-world; and finally the earliest stages from the simple prebiotic systems to RNA. The triplicase/proto-ribosome theory for the origin of the ribosome is discussed where triples of nucleotides are added to a replicating RNA, with the origin of a triplet code well-before protein synthesis begins. The length of the code is suggested to arise from the early development of a ratchet mechanism that overcomes the problem of continued processivity of an RNA-based RNA-polymerase. It is probable that there were precursor stages to RNA with simpler sugars, or just two nucleotides, but we do not yet know of any better alternatives to RNA that were likely to arise naturally. For prebiotic stages (before RNA) a flow-reactor model is suggested to solve metabolism, energy gradients, and compartmentation simultaneously – thus the intense interest in some form of flow reactor. If an autocatalytic cycle could arise in such a system we would be major steps ahead. The most likely physical conditions for the origin of life require further clarification and it is still unclear whether the origin of life is more of an entropy (information) problem (and therefore high temperatures would be detrimental), rather than a kinetic problem (where high temperatures may be advantageous). (shrink)

This paper investigated the part played by collaborative practices in chaneling the work of prominent biochemists into the development of molecular biology. The RNA collaborative network that emerged in the 1960s in France encompassed a continuum of activities that linked laboratories to policy-making centers. New institutional frameworks such as the DGRST committees were instrumental in establishing new patterns of funding, and in offering arenas for multidisciplinary debates and boundary assessment. It should be stressed however, that although this collaborative network was (...) based on centralized initiatives aimed at developing molecular biology as a new biological specialty, it operated above all as a nexus of practices. The main argument of this paper is that the central allocation of funds and resources, exemplified by the DGRST operation, actually enhanced the creation of a self-conscious community of biochemists turned molecular biologists by virtue of an increased circulation of tools, skills, and results that took place within the RNA network and a few analogous systems of exchange.Having hands on “things” viewed as identical for all practical purposes was a potent factor in changing the experimental systems and their meanings. Limited but shared means of doing helped to reduce uncertainties, change representations, and turn contingent decisions into meaningful choices. The collaborative enterprises then resulted in personal contacts and the transfer of skills and materials, which gradually incorporated the biochemical tools into systems producing facts relevant to molecular biology as defined by its early practitioners. In that sense, networking was a regulatory process that stabilized new research objects and acculturated French biochemists.The mere existence of such a collaborative network also changed the scale of the disciplining process. Collaborations may have been started for contingent motives, but multiple exchanges resulted in the emergence of a new collective, and amplified small displacements. Collaborations, however, worked both ways, and the RNA network may be viewed as an efficient “trading-post.” An unexpected outcome of the development of a conversion zone is the fact that, by the late 1960s, the former biochemists dominated the “new” world of molecular biology — both in terms of research habits, since interests in structural studies dominated the field, and in terms of institutional initiatives such as the creation of laboratories and institutes for molecular biology.As an example of the cognitive displacements achieved by the network, I have focused here on the stabilization of “messenger RNA” as a new biological entity. This process illustrates the role of “boundary objects” and other mediating innovations in the development of disciplinary structures. Students of science trained in the symbolic interactionism tradition have proposed that “boundary objects” enhance the multiple interactions between heterogeneous social worlds: they are robust enough to enhance unity, but plastic enough to be manipulated in different social and cultural contexts.81 Within the emerging network, messenger RNA was a weakly structured “genetic information carrier” in common use, but it could, at the same time, be a strongly structured “macromolecular structure” adapted to practical and local uses. Consequently, messenger RNA favored the association of groups of heterogeneous scientists with backgrounds and interests in medical biochemistry, genetics, physical chemistry, organic chemistry, and so forth. This contrast between general and local uses was also instrumental in integrating the manipulation of things and the negotiation of aims. In contrast to transfer RNAs, which in the French context remained objects for chemical (and mainly structural) studies, messenger RNA became a key component of the new culture of “genetic information”. Messenger RNA was a loose theoretical entity described as a “genetic information carrier” in the policy-making documents, while operational but tacit and more conflicting definitions prevailed at the bench. In other words, messenger RNA was not only a classical “boundary object” but also a “flag object,” which tightened the collaborative network by mediating between the DGRST offices and the laboratories. (shrink)

Knowing how introns originated should greatly enhance our understanding of the information we carry in our DNA. Gilbert’s suggestion that introns initially arose to facilitate recombination still stands, though not for the reason he gave. Reanney’s alternative, that evolution, from the early “RNA world” to today’s DNA-based world, would require the ability to detect and correct errors by recombination, now seems more likely. Consistent with this, introns are richer than exons in the potential to extrude the stem-loop structures (...) needed for the homology search that can lead to heteroduplex formation and the recognition of base mismatches. In nucleic acid sequences that were unable concomitantly to encode sufficient stem-loop potential, protein-encoding potential was constrained to arise as segments (exons) interrupted by segments rich in stem-loop potential (introns). Thus, sequences with properties that we now deem intronic are likely to have preceded the emergence of exons. (shrink)

The relational structure of RNA, DNA, and protein bears an interesting similarity to the determination problem in category theory. In this paper, we present this deep-structure similarity and use it as a springboard for discussing some abstract properties of coding in various systems. These abstract properties, in turn, may shed light on the evolution of the DNA world from a semiotic perspective. According to the perspective adopted in this paper, living systems are not information processing systems but “meaning-making” systems. (...) Therefore, what flows in the genetic system is not “information” but “value.” We define meaning, meaning-making, and value and then use these terms to explain the abstract dynamics of coding, which can illuminate many forms of sign-mediated activities in biosystems. (shrink)

We address the need for a model by considering two competing theories regarding the origin of life: (i) the Metabolism First theory, and (ii) the RNA World theory. We discuss two interrelated points, namely: (i) Models are valuable tools for understanding both the processes and intricacies of origin-of-life issues, and (ii) Insights from models also help us to evaluate the core objection to origin-of-life theories, called “the inefficiency objection”, which is commonly raised by proponents of both the Metabolism First (...) theory and the RNA World theory against each other. We use Simpson’s Paradox (SP) as a tool for challenging this objection. We will use models in various senses, ranging from taking them as representations of reality to treating them as theories/accounts that provide heuristics for probing reality. In this paper, we will frequently use models and theories interchangeably. Additionally, we investigate Conway’s Game of Life and contrast it with our SP-based approach to emergence-of-life issues. Finally, we discuss some of the consequences of our view. A scientific model is testable in three senses: (i) a logical sense, (ii) a nomological sense, and (iii) a current technological sense. The SP-based model is testable in the first two senses but it is not feasible to test it using current technology. (shrink)

Recent investigations surprisingly indicate that single RNA "stem-loops" operate solely by chemical laws that act without selective forces, and in contrast, self-ligated consortia of RNA stem-loops operate by biological selection. To understand consortial RNA selection, the concept of single quasi-species and its mutant spectra as drivers of RNA variation and evolution is rethought here. Instead, we evaluate the current RNA world scenario in which consortia of cooperating RNA stem-loops are the basic players. We thus redefine quasispecies as RNA quasispecies (...) consortia and argue that it has essential behavioral motifs that are relevant to the inherent variation, evolution and diversity in biology. We propose that qs-c is an especially innovative force. We apply qs-c thinking to RNA stem-loops and evaluate how it yields altered bulges and loops in the stem-loop regions, not as errors, but as a natural capability to generate diversity. This basic competence-not error-opens a variety of combinatorial possibilities which may alter and create new biological interactions, identities and newly emerged self identity functions. Thus RNA stem-loops typically operate as cooperative modules, like members of social groups. From such qs-c of stem-loop groups we can trace a variety of RNA secondary structures such as ribozymes, viroids, viruses, mobile genetic elements as abundant infection derived agents that provide the stem-loop societies of small and long non-coding RNAs. (shrink)

A replicator is simply something that makes copies of itself. There are hypothetical replicators (e.g., self-catalyzing chemical cycles) that are suspected to be unable to exhibit heritable variation. Variation in any of their constituent molecules would not lead them to produce offspring with those new variant molecules. Copying, such as in DNA replication or in xerox machines, allows any sequence to be remade and then sequence variations to be inherited. This distinction has been used against non-RNA-world hypotheses: without RNA (...) replication systems have no capacity to exhibit heritable variation. However, is copying the only way to have heritable variation? This article suggests that evolution can happen without anything being copied and that, in fact, RNA copying is too complex to arise spontaneously as the first pre-biotic system. There would then be a historical gradation of systems from non-alive to alive in which the capacity to have heritable changes would progressively increase and in which copying, as in template-based RNA-replication, would be a crucial but relatively late event. In addition, this article proposes a way by which RNA replication could have arisen, after systems able to evolve arose, as a crucial innovation and how that innovation spread over existing evolutionary systems and became a major driver of subsequent evolution. (shrink)

Despite their seemingly endless diversity, proteins adopt a limited number of structural forms. It has been estimated that 80% of proteins will be found to adopt one of only about 400 folds, most of which are already known. These folds are largely formed by a limited ‘vocabulary’ of recurring supersecondary structure elements, often by repetition of the same element and, increasingly, elements similar in both structure and sequence are discovered. This suggests that modern proteins evolved by fusion and recombination from (...) a more ancient peptide world and that many of the core folds observed today may contain homologous building blocks. The peptides forming these building blocks would not in themselves have had the ability to fold, but would have emerged as cofactors supporting RNA‐based replication and catalysis (the ‘RNA world’). Their association into larger structures and eventual fusion into polypeptide chains would have allowed them to become independent of their RNA scaffold, leading to the evolution of a novel type of macromolecule: the folded protein. BioEssays 25:837–846, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The problem of how a mixture of chemicals can spontaneously transform themselves into even a simple living organism remains one of the great outstanding challenges to science. Various primordial soup theories have been proposed in which chemical self- organization brings about the required level of complexity. Major conceptual obstacles remain, however, such as the emergence of the genetic code, and the “chicken-and-egg” problem concerning which came first: nucleic acids or proteins. Currently fashionable is the so-called RNA world theory, which (...) casts RNA in the role of both chicken and egg. Other theories assume that protein chemistry and even clay crystal life came before nucleic acids. To be fully successful, a theory of biogenesis has to explain not merely the emergence of molecular replication and chemical complexity, but the crucial information content and information processing capabilities of the living cell. (shrink)

Protein redox reactions are one of the most basic and important biochemical actions. As amino acids are weak redox mediators, most protein redox functions are undertaken by protein cofactors, which include organic ligands and transition metal ions. Since both kinds of redox cofactors were available in the pre‐protein RNA world, it is challenging to explore which one was more involved in redox processes of primitive proteins? In this paper, using an examination of the redox cofactor usage of putative ancient (...) proteins, we infer that organic ligands participated more frequently than transition metals in redox reactions of primitive proteins, at least as protein cofactors. This is further supported by the relative abundance of amino acids in the primordial world. Supplementary material for this article can be found on the BioEssays website. BioEssays 30:766–771, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

The three processes needed to create life, compartmentalization, metabolism, and information transfer (memory stored in nucleic acids and manipulation operated by proteins) are embedded in organized genome features. The core of life puts together growth and maintenance (which drives survival), while life in context explores and exploits specific niches. Analysis of gene persistence in a large number of genomes shows that the former constitutes the paleome, which recapitulates the three phases of the origin of life: metabolism of small molecules on (...) surfaces, substitution of surfaces by an RNA-world where transfer RNA played a central role, and invention of template mediated information transfer. Colonization of each niche is performed using an almost unlimited set of genes, forming the cenome. The agreement of the paleome structure with a consistent scenario for the origin of life is such that we may consider extant genomes as providing us with an archive of the origin rather than as a palimpsest where most of our past would be irremediably hidden. (shrink)

Prokaryotes are generally assumed to be the oldest existing form of life on earth. This assumption, however, makes it difficult to understand certain aspects of the transition from earlier stages in the origin of life to more complex ones, and it does not account for many apparently ancient features in the eukaryotes. From a model of the RNA world, based on relic RNA species in modern organisms, one can infer that there was an absolute requirement for a high-accuracy RNA (...) replicase even before proteins evolved. In addition, we argue here that the ribosome (together with the RNAs involved in its assembly) is so large that it must have had a prior function before protein synthesis. A model that connects and equates these two requirements (high-accuracy RNA replicase and prior function of the ribosome) can explain many steps in the origin of life while accounting for the observation that eukaryotes have retained more vestiges of the RNA world. The later derivation of prokaryote RNA metabolism and genome structure can be accounted for by the two complementary mechanisms of r-selection and thermoreduction. BioEssays 21:880–889, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

The central dogma of molecular biology dictates that, with only a few exceptions, information proceeds from DNA to protein through an RNA intermediate. Examining the enigmatic steps from prebiotic to biological chemistry, we take another road suggesting that primordial peptides acted as template for the self-assembly of the first nucleic acids polymers. Arguing in favour of a sort of archaic “reverse translation” from proteins to RNA, our basic premise is a Hadean Earth where key biomolecules such as amino acids, polypeptides, (...) purines, pyrimidines, nucleosides and nucleotides were available under different prebiotically plausible conditions, including meteorites delivery, shallow ponds and hydrothermal vents scenarios. Supporting a protein-first scenario alternative to the RNA world hypothesis, we propose the primeval occurrence of short two-dimensional peptides termed “selective amino acid- and nucleotide-matching oligopeptides” (henceforward SANMAOs) that noncovalently bind at the same time the polymerized amino acids and the single nucleotides dispersed in the prebiotic milieu. In this theoretical paper, we describe the chemical features of this hypothetical oligopeptide, its biological plausibility and its virtues from an evolutionary perspective. We provide a theoretical example of SANMAO’s selective pairing between amino acids and nucleosides, simulating a poly-Glycine peptide that acts as a template to build a purinic chain corresponding to the glycine’s extant triplet codon GGG. Further, we discuss how SANMAO might have endorsed the formation of low-fidelity RNA’s polymerized strains, well before the appearance of the accurate genetic material’s transmission ensured by the current translation apparatus. (shrink)

The term biology is of Greek origin meaning the study of life. On the other hand, chemistry is the science of matter, which deals with matter and its properties, structure, composition, behavior, reactions, interactions and the changes it undergoes. The theory of abiogenesis maintains that chemistry made a transition to biology in a primordial soup. To keep the naturalistic ‘inanimate molecules to human life’ evolution ideology intact, scientists must assemble billions of links to bridge the gap between the inanimate chemicals (...) that existed in the primordial soup and anatomically modern humans. Even though the proponents of a natural origin of life expressed much optimism for providing their theories, presently there is a detailed compilation of information seriously questioning this doctrine. This reductionistic ideology has always failed to answer two simple questions: (1) What is the minimum number of parts that are essential for a living organism to survive? (2) By what mechanism do these parts get assembled together? Evolutionists say a series of prebiotic processes and developments guide networks of dynamically linked small molecules and amphiphiles to form biological macromolecules, membraneous compartments, and finally primitive cells. However, none of these proposed pathways to life appears to be credible. The continuous advancement in various fields of science are not only providing major challenges to reductionistic ideology but are supplying increasing evidence for a systemic concept of life as an organic whole. Several leading researchers in the field of ‘origin of life’ are continually concluding that there are major scientific problems attached with all existing naturalistic ‘origin of life’ hypothesis. Only by taking into account all biological activities collectively as a system can a satisfactory elucidation of the living state be realized. In this present paper an attempt has been made to present a few significant challenges to the theory of abiogenesis based on the peer reviewed scientific literature. Subsequently, a non-reductionistic concept of life as a system is proposed as an alternative for resolving some of the problems inherent in origin of life research. (shrink)

This paper calls attention to a philosophical presupposition, coined here the continuity thesis which underlies and unites the different, often conflicting, hypotheses in the origin of life field. This presupposition, a necessary condition for any scientific investigation of the origin of life problem, has two components. First, it contends that there is no unbridgeable gap between inorganic matter and life. Second, it regards the emergence of life as a highly probable process. Examining several current origin-of-life theories. I indicate the implicit (...) or explicit role played by the continuity thesis in each of them. In addition, I identify the rivals of the thesis within the scientific community — the almost miracle camp. Though adopting the anti-vitalistic aspect of the continuity thesis, this camp regards the emergence of life as involving highly improbable events. Since it seems that the chemistry of the prebiotic stages and of molecular self-organization processes rules out the possibility that life is the result of a happy accident, I claim that the almost miracle view implies in fact, a creationist position. (shrink)

The ‘managed-metabolism’ hypothesis suggests that a ‘cooperation barrier’ must be overcome if self-producing chemical organizations are to undergo the transition from non-life to life. This dynamical barrier prevents un-managed autocatalytic networks of molecular species from individuating into complex, cooperative organizations. The barrier arises because molecular species that could otherwise make significant cooperative contributions to the success of an organization will often not be supported within the organization, and because side reactions and other ‘free-riding’ processes will undermine cooperation. As a result, (...) the barrier seriously impedes the emergence of individuality, complex functionality and the transition to life. This barrier is analogous to the cooperation barrier that also impedes the emergence of complex cooperation at all levels of living organization. As has been shown at other levels of organization, the barrier can be overcome comprehensively by appropriate ‘management’. Management implements a system of evolvable constraints that can overcome the cooperation barrier by ensuring that beneficial co-operators are supported within the organization and by suppressing free-riders. In this way, management can control and manipulate the chemical processes of a collectively autocatalytic organization, producing novel processes that serve the interests of the organization as a whole and that could not arise and persist in an un-managed chemical organization. Management self-organizes because it is able to capture some of the benefits that are produced when its interventions promote cooperation, thereby enhancing productivity. Selection will therefore favour the emergence of managers that take over and manage chemical organizations so as to overcome the cooperation barrier. The managed-metabolism hypothesis demonstrates that if management is to overcome the cooperation barrier comprehensively, its interventions must be digitally coded. In this way, the hypothesis accounts for the two-tiered structure of all living cells in which a digitally-coded genetic apparatus manages an analogically-informed metabolism.GraphicalOpen image in new window. (shrink)

Biological modalities, i.e., biologically possible, impossible, or necessary states of affairs have not received much attention from philosophers. Yet, it is widely agreed that there are biological constraints on physically possible states of affairs, such that not everything that is physically possible is also biologically possible, even if everything that is biologically possible is also physically possible. Furthermore, biologists use concepts that appear to be modal in nature, such as the concept of evolvability in evolutionary developmental biology, or “evo-devo.” The (...) present chapter investigates what kind of modality underlies the concept of evolvability. This concept tries to capture the capacity of an organism or a lineage to sustain genetic changes that enable it to evolve or to evolve adaptively. The basic idea of the proposed approach is to construe evolvability as a kind of accessibility in a modal space. The difficult part is to specify this modal space and the relevant accessibility relation. While there may not be a general way of defining such a relation, there exist model systems for which it is possible, e.g., evolving small RNAs. The modal space in such cases turns out to be quite distinct from those constructed by philosophers, e.g., David Lewis’s similarity metric for possible worlds. Even though the biological case examined here is quite special, attending to the way in which biological possibilities are modeled in this case harbors some general lessons about biological modalities, in particular their dependence on the explanatory goals of the models modeling modality. (shrink)

This study explores the history of nanotechnology from the perspective of protein engineering, which differs from the history of nanotechnology that has arisen from mechanical and materials engineering; it also demonstrates points of convergence between the two. Focusing on directed evolution—an experimental system of molecular biomimetics that mimics nature as an inspiration for material design—this study follows the emergence of an evolutionary experimental system from the 1960s to the present, by detailing the material culture, practices, and techniques involved. Directed evolution, (...) as an aspect of nanobiotechnology, is also distinct from the dominant biotechnologies of the 20th century. The experimental systems of directed evolution produce new ways of thinking about molecular diversity that could affect concepts concerning both biology and life. (shrink)

In this paper, we present an argument showing why the general properties of a self-organizing system (e.g. being far from equilibrium) may be too weak to characterize biological and proto-biological systems. The special character of biological systems, tell us that its distinctive capacities could have been developed in pre-biotic times. In other words, the basic properties of life would be better comprehended if we think that they were much more likely early in time. We developed a conceptual proposal on the (...) origins of pre-biotic world, a kind of protocellular system which is made up of simple molecular compounds interconnecting three different types of processes. The interrelation of these processes characterizes the “Informational Dynamical System” (our conceptualprotocell proposal) as an autonomous dynamical system that can maintain by itself in far from equilibrium state, as opposed to those that depend on external causes. Consequently it follows that, in the dawn of pre-biotic world, there was no DNA or RNA or proteins to begin with. As well, our proposal implies the separation of biological evolution from the kind of open-ended evolution that gave rise to first breed of animate matter. (shrink)

Model organisms, the use of green fluorescent proteins, and orthogonal transfer RNA are examples of artificial causes being used in biology. Recent work characterizing the research interests of biologists in terms of a common set of values has ruled out artificial causes as biologically interesting. For instance, Kenneth Waters argues that biologists are primarily interested in causes that actually obtain. Similarly, Marcel Weber argues that biologists are primarily concerned with biologically normal interventions. Both views express a widely received attitude about (...) the interests and goals of biologists as being primarily concerned with the contingent facts of our world. While I agree with this general attitude about the contingent nature of biology, I argue that neither view fully accounts for the diversity that distinguishes the discipline. Along with actual and biologically normal causes, biologists are also interested in artificial causes for technological and observational purposes. I maintain that research interest in artificial causes provides some pragmatic reasons for thinking that research programs in cellular biology aren’t driven by a common core set of values. (shrink)

Our aim in this article is to attempt to discuss propagating organization of process, a poorly articulated union of matter, energy, work, constraints and that vexed concept, “information”, which unite in far from equilibrium living physical systems. Our hope is to stimulate discussions by philosophers of biology and biologists to further clarify the concepts we discuss here. We place our discussion in the broad context of a “general biology”, properties that might well be found in life anywhere in the cosmos, (...) freed from the specific examples of terrestrial life after 3.8 billion years of evolution. By placing the discussion in this wider, if still hypothetical, context, we also try to place in context some of the extant discussion of information as intimately related to DNA, RNA and protein transcription and translation processes. While characteristic of current terrestrial life, there are no compelling grounds to suppose the same mechanisms would be involved in any life form able to evolve by heritable variation and natural selection. In turn, this allows us to discuss at least briefly, the focus of much of the philosophy of biology on population genetics, which, of course, assumes DNA, RNA, proteins, and other features of terrestrial life. Presumably, evolution by natural selection—and perhaps self-organization—could occur on many worlds via different causal mechanisms. Here we seek a non-reductionist explanation for the synthesis, accumulation, and propagation of information, work, and constraint, which we hope will provide some insight into both the biotic and abiotic universe, in terms of both molecular self reproduction and the basic work energy cycle where work is the constrained release of energy into a few degrees of freedom. The typical requirement for work itself is to construct those very constraints on the release of energy that then constitute further work. Information creation, we argue, arises in two ways: first information as natural selection assembling the very constraints on the release of energy that then constitutes work and the propagation of organization. Second, information in a more extended sense is “semiotic”, that is about the world or internal state of the organism and requires appropriate response. The idea is to combine ideas from biology, physics, and computer science, to formulate explanatory hypotheses on how information can be captured and rendered in the expected physical manifestation, which can then participate in the propagation of the organization of process in the expected biological work cycles to create the diversity in our observable biosphere. Our conclusions, to date, of this enquiry suggest a foundation which views information as the construction of constraints, which, in their physical manifestation, partially underlie the processes of evolution to dynamically determine the fitness of organisms within the context of a biotic universe. (shrink)

Synthetic biologists try to engineer useful biological systems that do not exist in nature. One of their goals is to design an orthogonal chromosome different from DNA and RNA, termed XNA for xeno nucleic acids. XNA exhibits a variety of structural chemical changes relative to its natural counterparts. These changes make this novel information‐storing biopolymer “invisible” to natural biological systems. The lack of cognition to the natural world, however, is seen as an opportunity to implement a genetic firewall that (...) impedes exchange of genetic information with the natural world, which means it could be the ultimate biosafety tool. Here I discuss, why it is necessary to go ahead designing xenobiological systems like XNA and its XNA binding proteins; what the biosafety specifications should look like for this genetic enclave; which steps should be carried out to boot up the first XNA life form; and what it means for the society at large. (shrink)

Function talk is a constant across different life sciences. From macro-evolution to genetics, functions are mentioned everywhere. For example, a limb’s function is to allow movement and RNA polymerases’ function is to transcribe DNA. Biochemistry is not immune from such a characterization; the biochemical world seems to be a chemical world embedded within biological processes. Specifically, biochemists commonly ascribe functions to biomolecules and classify them accordingly. This has been noticed in the recent philosophical literature on biochemical kinds. But (...) while a lot has been written on biological and psychological functions, little has been said explicitly about biochemical fuctions. Here, I explore functional attribution to biochemical molecules. I argue that if we accept this attribution, then biochemical functions are constituted by chemical dispositional properties that causally contribute to selected biological processes. In section 2, I discuss the controversy concerning the characterization of biochemical functions. In section 3, I consider whether a biological or a chemical under- standing of function can be applied to biochemical functions, illustrating the account with the example of vitamin B12. The result is that none of the theories on their own provides an adequate characterization. In section 4, I present an account of biochemical functions. In section 5, I assess this account taking into consideration common requirements for a theory of functions and an objection. (shrink)

Rifamycin is a clinically useful macrolide antibiotic produced by the gram positive bacterium. Amycolatopsis mediterranei. This antibiotic is primarily used against Mycobacterium tuberculosis and Mycobacterium leprae, causative agents of tuberculosis and leprosy, respectively. In these bacteria, rifamycin treatment specifically inhibits the initiation of RNA synthesis by binding to β‐subunit of RNA polymerase. Apart from its activity against the bacteria, rifamycin has also been reported to inhibit reverse transcriptase (RT) of certain RNA viruses. Recently, rifamycin derivatives have been dis‐covered that are (...) effective against Mycobacterium avium, which is associated with the AIDS complex. Consequently, the importance of and demand for rifamycin has increased tremendously, the world over. In this article, recent trends in rifamycin research and accessability of recombinant DNA techniques to increase rifamycin production are reviewed. (shrink)

This year marks the tenth anniversary of the world's first transplantation of tissue generated from induced pluripotent stem cells (iPSCs). There is now a growing number of clinical trials worldwide examining the efficacy and safety of autologous and allogeneic iPSC‐derived products for treating various pathologic conditions. As we patiently wait for the results from these and future clinical trials, it is imperative to strategize for the next generation of iPSC‐based therapies. This review examines the lessons learned from the development (...) of another advanced cell therapy, chimeric antigen receptor (CAR) T cells, and the possibility of incorporating various new bioengineering technologies in development, from RNA engineering to tissue fabrication, to apply iPSCs not only as a means to achieve personalized medicine but also as designer medical applications. (shrink)

Poreskoro, with three cat and four dog heads and a snake with a forked tongue as his tail, is responsible for epidemics of contagious diseases in Romany folklore. The Pishachas of Vedic mythology lurk in charnel houses and graveyards, waiting for humans to infect with madness. In Christian demonology, Pythius is known as the ruler of the eighth circle of the Inferno, bestowing heinous and unspeakable tortures on those who have committed fraud. Demons are the stuff of legends, and they (...) are everywhere in mythology and theology. These are just three of the more than thirty I counted that start with the letter P.How lucky we are for the advent of science. A rational tonic, it scatters our demons, demystifying the world for us—or so, at least, we think. As Canales brilliantly shows in this book, our assumption has been far off the mark. In physics, computer science, genetics, neuroscience, and economics, not to mention in the very foundations of rationality itself, an underworld of imaginary creatures has sustained and continues to inhabit modern science. Scientific demons appear in many guises: as atomic and subatomic particle manipulators, as feedback and parallel-processing experts, as messengers who can travel faster than the speed of light, as computer-code spies, gene and bit selectors in evolution and in informatics, as triggers of cascades from the nano level to the level of full-blown ecological and astrophysical theaters. By inventing them, we have learned that causality does not always hold at the level of atoms, that the speed of message transmission is limited, that living systems spend energy, that perpetual-motion machines are impossible, and that there are corners of the universe we have not imagined.We have all heard of Laplace's Demon, and Maxwell's, but who knew that, borrowing from physics, the historian Henry Adams considered the action of demons in geopolitics or that the economist Paul Samuelson analyzed their role in producing more efficient markets? Who knew that the generation that gave us the Internet and artificial intelligence were tasked by their teachers in graduate school to insert as many demons as possible into their programs? Who among us has heard of Darwin's Demon, or Maxwell-Szilárd-Brillouin's, or Monod's, or Loschmidt's? Who is aware of Norbert Weiner's use of demons in conceptualizing cybernetics, or of the great scholar of Kabbalah Gershom Scholem's comparison between Israel's superfast computers and the Golem?As Canales shows convincingly, it has been difficult for both historians and scientists to countenance demons in science, and so they have been written out, in many ways and many instances, of the histories of which they are part and parcel. Thomas Kuhn and even the more radical philosopher Paul Feyerabend both failed to acknowledge in their social critiques of science the extent to which an imaginary underworld of beings has been constitutive of the modern scientific imagination. Ironically, it was the man who provided a hard-and-fast criterion by which to distinguish scientific and nonscientific pursuits, Karl Popper, who ultimately saw the light. Revisiting his classic book The Logic of Scientific Discovery from 1934, he clarified in Postscript to the Logic of Scientific Discovery in 1982 the extent to which every historical era has been characterized by a particular demon. We moderns believe that science is about facts and numbers, but we are mistaken. As Canales beautifully summarizes the stakes of her project, “What first sets science on its path of discovery—then as now—is the continued use of the imagination.”Tracking the fate of demons in modern thought from Descartes to Lord Kelvin to H. G. Wells to David Bohm, and from Conrad Hal Waddington to Henry Compton to Stephen Hawking and Steven Pinker, Bedeviled assumes that the demons of the church or of paganism and the demons of science differ and resemble each other in ways that can be usefully elaborated. What is more crucial, however, is how such demons become real, how they morph from fears to hopes, and from thought experiments into real experiments, and ultimately to things in this world like computer programs, transistors, and nanorobots. From weather systems to messenger RNAs to black holes, demons emerge everywhere. The hard question is: How does the imagination actually drive discovery and understanding? How does it change our world?Perhaps it has been a sidetrack to consider whether we have or have never been modern. Clearly, what reason will not allow, it perennially recruits for a shadowland that helps us to better see our world. Rather than aiming to exorcise science, one day, of all of its methodological and epistemological ghosts, perhaps we might make peace with the notion that every culture struggles with distinguishing truth from falsehood in its own unique way. Such struggles are sensitive to their times and are accomplished through leaps of imagination. But fear not: the debunking of “Western rationality” casts no wet blanket on the project of Enlightenment. If anything, as Canales writes, “an account of science that considers how scientists themselves do science only risks adding new insights into our repertoire of knowledge.” Perhaps, therefore, there is solace to be gained from the dictum, Always choose the Devil you know. Ultimately, there may be no other way forward. (shrink)

This essay moves along broad lines from molecular biology to evolutionary biology and ecology to theology. Its objectives are to: 1) present some recent scientific findings in the emerging field of epigenetics that indicate that it is “the genome in context,” not genes per se, that are important in biological development and evolution; 2) show that this weakens the gene-centric neo-Darwinist explanation of evolution which, in fact, shares a certain preformationist orientation with intelligent design theory; 3) argue that the evidence (...) against a gene-centric view in no way negates Darwin’s central idea of “descent with modification”; 4) argue that an embrace of the evolutionary story, with all of its contingency and apparent lack of directionality, is not only consistent with Christianity, but actually resonates with the notion of the self-emptying love of God in Jesus Christ; and finally 5) suggest that we are called through an ecological imperative to embrace our evolutionary story, to listen to our “genetic coding,” and to reclaim our grounding as a species in the natural world. Corrigendum (published in later issue of journal): There was an error in the paragraph describing the mode of action of the small temporally-expressed RNAs (stRNAs) lin-4 and let-7 from Caenorhabditis elegans. Instead of reading "These two stRNAs act by binding to the tails of their target messenger RNAs (mRNAs); this results in destruction of the target and an overall drop in the level of production of protein from agouti mRNA" [note that agouti mRNA is not a target of these stRNAs], the sentence should have read, "These two stRNAs act by binding to the tails of target messenger RNAs (mRNAs); this leads to inhibition of translation of the mRNAs into protein and a consequent drop in the levels of the corresponding target protein.". (shrink)

The complexity of intracellular molecular pathways can be simplified by the use of Network Biology that breaks down the intricacy of biological processes into components and interactions among them. In the paper we show that any complex interactome, that is, a biological network representing protein-protein, protein-DNA and DNA-RNA interactions, can be decomposed into a conjunction of logical theorems expressed in terms of Zsyntax, a formal language which allows representing biological pathways. This result, illustrated with the case study of melanoma network, (...) opens the possibility for a computable model of the cell expressed in a logical language and shows how a formal way of intending philosophy can be useful to cope with the complexity of the biological world. (shrink)

New concepts may prove necessary to profit from the avalanche of sequence data on the genome, transcriptome, proteome and interactome and to relate this information to cell physiology. Here, we focus on the concept of large activity-based structures, or hyperstructures, in which a variety of types of molecules are brought together to perform a function. We review the evidence for the existence of hyperstructures responsible for the initiation of DNA replication, the sequestration of newly replicated origins of replication, cell division (...) and for metabolism. The processes responsible for hyperstructure formation include changes in enzyme affinities due to metabolite-induction, lipid-protein affinities, elevated local concentrations of proteins and their binding sites on DNA and RNA, and transertion. Experimental techniques exist that can be used to study hyperstructures and we review some of the ones less familiar to biologists. Finally, we speculate on how a variety of in silico approaches involving cellular automata and multi-agent systems could be combined to develop new concepts in the form of an Integrated cell (I-cell) which would undergo selection for growth and survival in a world of artificial microbiology. (shrink)

The Pfizer-BioNTech coronavirus vaccine is 90 percent effective in protecting against COVID-19. It would not have been possible without the tireless effort of Professor Katalin Karikó, a scientific innovator fitting the mold of dynamic inventor Arthur Diamond presents in his book, Openness to Creative Destruction Sustaining Innovative Dynamism. Not only did Professor Karikó persist in her beliefs in the therapeutic potential of synthetic messenger RNA over the course of four decades, but she did so despite the criticisms of other scientists (...) and despite lack of financial backing for large parts of her career. Professor Karikó is a good example of the unconventional picture that Diamond paints of entrepreneurs in a specific version of market capitalism he terms, innovative dynamism. Specifically, she is an example of someone who does not hold prevailing academic theories in too high a regard and instead privileges her tacit knowledge (knowledge gained from years of working with mRNA in the lab) to persist believing in the potential of a therapy that now could quite literally save the world. Most surprisingly, she, like most of the entrepreneurs surveyed in the book, seem not primarily motivated by profit, though the money their projects eventually attract is integral to disseminating their creative ideas to the masses. -/- Are the many examples offered by Diamond that are similar to Professor Karikó’s story evidence against the long-standing suspicion that there is something morally damning in the self-interested motivations of innovative entrepreneurship? Is it the case that others would have inevitably pursued the cure that Karikó pursued, regardless of economic system? In light of COVID-19 and other high-pressure situations, ought we to care how we constrain the innovators who develop solutions? Diamond’s case for the economic system, innovative dynamism, seeks to answer these and other important questions concerning our political and cultural treatment of innovators and entrepreneurs. This review critically assesses his efforts. I make my case by first reviewing the major argumentative structure of the book, then I summarize and evaluate the three major themes Diamond presents in the book: (1) what is innovative dynamism and who are its competitors, (2) what are the major benefits of innovative dynamism, (3) who is the innovative entrepreneur and how do we support him or her? (shrink)

Open theism denies that God has definite exhaustive foreknowledge, and affirms that God takes certain risks when creating the universe. Critics of open theism often complain that the risks are too high. Perhaps there is something morally wrong with God taking a risk in creating a universe with an open future. Open theists have tried to respond by clarifying how much risk is involved in God creating an open universe, though we argue that it remains unclear how much risk is (...) actually involved. We claim that open theists need to start developing theories about how God manages risks in order to bring about His purposes for the universe. In this article, we will take a philosophical and biological perspective on risk management that adds plausibility to open theism. We will consider how God can use different risk‐management, surveillance, and redundancy systems in the natural world in order to accomplish His goals. (shrink)

Adi Da argues that no solutions currently proposed are sufficient to righten the present unsustainable trajectory of life on Earth, because there is no integrated approach to the ordering of society and use of the planet. The presumption of separateness—manifesting collectively as separate “tribes” vying for control—characterizes human affairs, rather than the prior (“a priori”) unity of existence. The struggle for dominance is the “stave in the wheels” of the Earth-system's inherent capacity to self-correct. A new institution, “the Global Cooperative (...) Forum,” is proposed—invoked by “everybody-all-at-once” (a global populace awakened as a single force, capable of cooperatively effecting global change). (shrink)